Abstract |
The peroxisome proliferator-activated receptor ( PPAR)gamma is expressed not only in adipose tissue but also in macrophages/monocytes and plays important roles in acute/chronic inflammation. Transforming growth factor ( TGF)-beta is a common pathogenic indicator of sclerosis because it induces the accumulation of extracellular matrix (ECM) in the glomerular mesangium of the kidney. Among components of the ECM, fibronectin (FN) is an acute reactant in inflammation, and isoforms of it produced by splicing of gene variants appear during abnormal conditions such as wound healing. In this study, we examined the effects of pioglitazone, a PPARgamma agonist, on TGF-beta(1)-induced FN synthesis in cultured mesangial cells using RT-PCR and Western blot analysis. We also analyzed its splicing variant, extra domain (ED) A, containing FN ( EDA(+)FN). TGF-beta(1) enhanced the production of both FN and EDA(+) FN and down-regulated PPARgamma expression. Pioglitazone reversed both these effects of TGF-beta(1). These findings suggest that PPARgamma activation by pioglitazone may affect the TGF-beta(1)-induced FN accumulation observed in the glomerular mesangium in cases of glomerulosclerosis, although further in vivo experiments are needed to evaluate this inference.
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Authors | Atsuko Maeda, Satoshi Horikoshi, Tomohito Gohda, Toshinao Tsuge, Kunimi Maeda, Yasuhiko Tomino |
Journal | Cell biology international
(Cell Biol Int)
Vol. 29
Issue 6
Pg. 422-8
(Jun 2005)
ISSN: 1065-6995 [Print] England |
PMID | 16054559
(Publication Type: Journal Article)
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Chemical References |
- Fibronectins
- PPAR gamma
- Thiazolidinediones
- Transforming Growth Factor beta
- Pioglitazone
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Topics |
- Alternative Splicing
(drug effects, genetics)
- Cells, Cultured
- Fibronectins
(biosynthesis, genetics)
- Glomerular Mesangium
(cytology, drug effects, metabolism)
- Humans
- PPAR gamma
(genetics, metabolism)
- Pioglitazone
- Thiazolidinediones
(pharmacology)
- Transforming Growth Factor beta
(antagonists & inhibitors, pharmacology)
- Up-Regulation
(drug effects)
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